IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice

Yuejin Liang, Zuliang Jie, Lifei Hou, Panpan Yi, Wei Wang, Zakari Kwota, Maria Salvato, Rene de Waal Malefyt, Lynn Soong, Jiaren Sun

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Recent studies have revealed IL-33 as a key factor in promoting antiviral T-cell responses. However, it is less clear as to how IL-33 regulates innate immunity. In this study, we infected wild-type (WT) and IL-33<sup>-/-</sup> mice with lymphocytic choriomeningitis virus and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-γ production in the liver. We first show that IL-33 deficiency resulted in a marked reduction in the number of IFN-γ<sup>+</sup> γδ T and NK cells, but an increase in that of IL-17<sup>+</sup> γδ T cells at 16 h postinfection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-γ-producing γδ T and NK cells, and inhibiting IL-17<sup>+</sup> γδ T cells. We also found that rIL-33-induced type 2 innate lymphoid cells were not involved in T-cell responses and liver injury, since the adoptive transfer of type 2 innate lymphoid cells neither affected the IFN-γ and TNF-α production in T cells, nor liver transferase levels in lymphocytic choriomeningitis virus infected mice. Interestingly, we found that while IL-33 was not required for costimulatory molecule expression, it was critical for DC proliferation and cytokine production. Together, this study highlights an essential role of IL-33 in regulating innate IFN-γ-production and DC function during viral hepatitis.

Original languageEnglish (US)
JournalEuropean Journal of Immunology
DOIs
StateAccepted/In press - 2015

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Lymphocytic choriomeningitis virus
Dendritic Cells
Hepatitis
T-Lymphocytes
Interleukin-17
Natural Killer Cells
Liver
Lymphocytes
Interleukin-33
Adoptive Transfer
Transferases
Innate Immunity
Antiviral Agents
Cytokines

Keywords

  • Dendritic cell
  • IFN-γ
  • IL-33
  • Innate lymphoid cell
  • LCMV
  • Viral hepatitis
  • γδ T cell

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice. / Liang, Yuejin; Jie, Zuliang; Hou, Lifei; Yi, Panpan; Wang, Wei; Kwota, Zakari; Salvato, Maria; de Waal Malefyt, Rene; Soong, Lynn; Sun, Jiaren.

In: European Journal of Immunology, 2015.

Research output: Contribution to journalArticle

Liang, Yuejin ; Jie, Zuliang ; Hou, Lifei ; Yi, Panpan ; Wang, Wei ; Kwota, Zakari ; Salvato, Maria ; de Waal Malefyt, Rene ; Soong, Lynn ; Sun, Jiaren. / IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice. In: European Journal of Immunology. 2015.
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